Posted on July 17, 2015
With the regulatory and legislative environment surrounding compounding pharmacies undergoing substantial change, sterile compounding industry expert Eric S. Kastango, MBA, BS Pharm., FASHP, recently provided a webinar update on the new developments for pharmacists. The webinar reviewed recent contamination events associated with compounding pharmacies, the Food and Drug Administration (FDA)’s increase in facility investigations in the last three years, and how the Drug Quality and Safety Act (DQSA) affects pharmacies.
Kastango noted that since 2001, more than 25 pharmacy compounding incidents associated with 1,049 adverse events and 89 deaths have been reported. The most common errors involved contamination of sterile preparations; the most notable event was the 2012 NECC fungal meningitis contamination of steroid medications that affected 751 people, killing 64. Despite intense regulatory and media attention on sterile compounding standards after that incident, serious incidents regarding compounding pharmacies have occurred in multiple states including the closing of a New Jersey pharmacy and outbreak of Burkholderia linked to IV fentanyl at Duke University Hospital.
Just 27 states require direct compliance with U.S. (USP) Pharmacopeia 797, the nationally enforceable chapter regarding sterile compounding that was adopted in 2004. In the absence of standardized state regulation, the FDA has increased its inspections of compounding pharmacies. Since October 1, 2012, the FDA has conducted more than 170 inspections of compounding pharmacies and outsourcing facilities and issued more than 140 Form FDA-483s noting significant shortcomings. In addition, 27 compounding pharmacies and seven outsourcing facilities have received warning letters and one compounding pharmacy entered into a consent decree of permanent injunction.
Until the passage of the DQSA in November 2013, the FDA’s ability to take enforcement action was hamstrung by questions about its jurisdiction over compounding pharmacies. The DQSA clarified the role of the FDA, called for improved communication between the FDA and state boards of pharmacy, and enabled compounding pharmacies to register as “outsourcing facilities” subject to risk-based inspection and Current Good Manufacturing Practices (CGMP)–which can be substantially more rigorous than those detailed in USP 797. These pharmacies manufacture and ship larger quantities of compounded drugs across state lines without prescriptions.
Kastango said that as of May 17, 2015, 52 firms have registered as 503B outsourcing facilities. Of those, 44 had been inspected and 43 had received an FDA Form 483. The most commonly reported shortcomings observed by the FDA in these outsourcing facilities were:
Issues with improper environmental monitoring
Failure to subject terminally sterilized preparations to a validated sterilization cycle
Insufficient lab testing (particularly for potency or USP 71 sterility)
Lack of procedures to prevent microbial contamination
Insufficient data on stability of preparations stored for extended periods
Batch release of sterile product without sufficient testing
Failure to ensure adequacy of equipment used in compounding
Inadequate facility/smoke studies for air balance and airflow
Improper cleaning or disinfection
Inappropriate response to problems or errors
Failure to perform or follow up on endotoxin testing.
In conclusion, Kastango added that state boards of pharmacy are responding to the challenges of overseeing traditional (503A) compounding pharmacies, even as the FDA takes control of those registered as outsourced facilities and those operating as manufacturers. He noted that proper training and the full commitment of employees to good work practices are essential for maintaining compliance. Compounding facilities must be correctly configured and well maintained as well as regularly assessed using environmental sampling to ensure the facility meets the required standards for sterile compounding.
FDA Inspections of Compounding Pharmacies
Table excerpted from: Eisler P and Schmaars C. Safety, sanitary problems prompt scores of drug recalls. USA Today. October 7, 2014 retrieved from